Deferment of objective assessment of deep vein thrombosis and pulmonary embolism without increased risk of thrombosis: a practical approach based on the pretest clinical model, D-dimer testing, and the use of low-molecular-weight heparins

BACKGROUND: Treatment of patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) is problematic if diagnostic imaging is not immediately available. Pretest clinical probability (PCP) and D-dimer assessment can be used to identify patients for whom empirical protective anticoagulation is indicated. To evaluate whether PCP and D-dimer assessment, together with the use of low-molecular-weight heparins (LMWHs), allow objective appraisal of DVT and PE to be deferred for up to 72 hours, patients with suspected DVT and PE were prospectively examined. METHODS: Patients identified with a high PCP or a moderate PCP with positive D-dimer test results received a protective full-dose treatment of LMWH; the remaining patients were discharged without anticoagulant administration. However, all patients were scheduled to undergo objective tests for DVT or PE within 72 hours. Standard antithrombotic therapy was administered when deferred diagnostic tests confirmed venous thromboembolism. RESULTS: In total, 409 consecutive patients with suspected DVT and 124 with suspected PE were included in this study. A total of 23.8% (95% confidence interval [CI], 20.3%-27.3%) of patients had confirmed venous thromboembolism. At the short-term follow-up (72 hours), only a single thromboembolic event (0.2%; upper 95% CI, 0.6%) had occurred, whereas at the 3-month follow-up, 5 events (1.2%; 95% CI, 0.2%-2.1%) had occurred in patients in whom diagnosis of DVT or PE had previously been ruled out. None of the patients had major bleeding events. Ninety percent of patients were treated as outpatients. CONCLUSION: Our study demonstrates that this approach allows the safe deferral of diagnostic procedures for DVT and PE for up to 72 hours.     

Secondary prevention of cryptogenic stroke in patients with patent foramen ovale: a systematic review and meta-analysis

The aim of our study is to compare patent foramen ovale (PFO) closure versus medical treatment and antiplatelet versus anticoagulant therapy in patients with cryptogenic stroke (CS) and PFO. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) of randomized trials. Primary outcomes are stroke or transient ischemic attack (TIA) and all-cause mortality. Secondary outcomes are peripheral embolism, bleeding, serious adverse events, myocardial infarction and atrial dysrhythmias. We performed an intention to treat meta-analysis with a random-effects model. We include six trials (3677 patients, mean age 47.3 years, 55.8% men). PFO closure is associated with a lower recurrence of stroke or TIA at a mean follow-up of 3.88 years compared to medical therapy [risk ratio (RR) 0.55, 95% CI 0.38–0.81; I²?=?40%]. The TSA confirms this result. No difference is found in mortality (RR 0.74, 95% CI 0.35–1.60; I²?=?0%), while PFO closure is associated with a higher incidence of atrial dysrhythmias (RR 4.55, 95% CI 2.16–9.60; I²?=?25%). The rate of the other outcomes is not different among the two groups. The comparison between anticoagulant and antiplatelet therapy shows no difference in terms of stroke recurrence, mortality and bleeding. There is conclusive evidence that PFO closure reduces the recurrence of stroke or TIA in patients younger than 60 years of age with CS. More data are warranted to assess the consequences of the increase in atrial dysrhythmias and the advantage of PFO closure over anticoagulants.     

Myocardial perfusion in real-time using power modulation. In vivo evidence for microcirculatory damage after acute myocardial infarction

BACKGROUND: The effect of beta-radiation on extra-stent vascular remodeling in patients with in-stent restenosis has not been studied. The correlation between the extent of extra-stent plaque proliferation and that of intimal hyperplasia (IH) in in-stent restenosis in patients who received beta-radiation therapy as well as conventional therapy has also not been studied. METHODS: We evaluated the extra-stent remodeling in diffuse in-stent restenosis between a beta-radiation therapy patient group (188Re-MAG3, n=50) and a control group (n=9) by applying serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and follow-up) images were acquired at the follow-up lesion site and were available in 44 of 50 patients who received radiation therapy and in seven of nine control patients. RESULTS: There was a significant increase of the external elastic membrane (EEM) area in both groups: 16.4 +/- 3.3 mm2 post-intervention to 17.1 +/- 3.3 mm2 at follow-up, P=0.001 in the radiation therapy group, and 16.8 +/- 4.0 mm2 post-intervention to 17.4 +/- 4.1 mm2 at follow-up, P=0.008 in the control group. There were no statistically significant differences of the Delta EEM area between the two groups: 0.7 +/- 0.4 mm2 in the radiation therapy group vs. 0.6 +/- 0.4 mm2 in the control group, P=0.389. The Delta IH area correlated with the Delta EEM area in the control group (r=0.826, P=0.022), but not in the radiation therapy group (r=0.016, P=0.919). CONCLUSIONS: The findings of this IVUS study were that positive remodeling (increased EEM area) occurred equally in both control and irradiated patients with in-stent restenosis. The extent of remodeling was directly in proportion to IH in the control group, but no such relationship existed in the irradiated patient group.     

Influenza: the reemergence of an ancient disease and its risk of pandemia

Influenza is a seasonally, acute respiratory disease, highly transmissible. The diversity of the natural reservoirs of influenza A virus and its faculty of reassortment increase the risk of a new pandemia. Prevention strategies during the outbreaks include vaccination indicated to risk population as infants between 6 to 2 years old, persons above 65 years old, pregnant women and patients with underlying diseases. Antiviral prophylaxis is useful to control small outbreaks and to be used in household contacts of risk population who have not been vaccinated. Antiviral drugs as a treatment should be considered in persons with severe disease. During a pandemia these prevention measures must be reinforced and rational use of antiviral drugs and vaccine with the pandemic strain should be emphasized.     

Post-recurrence survival in hepatocellular carcinoma after percutaneous radiofrequency ablation

Background

Overall survival in hepatocellular carcinoma patients treated with percutaneous radiofrequency ablation is influenced by both recurrence and successive treatments. We investigated post-recurrence survival after radiofrequency ablation.

Methods

Data on 103 early/intermediate patients initially treated with radiofrequency ablation and followed for a median of 78 months (range 68–82) were retrospectively analysed. If intrahepatic disease recurrence occurred within or contiguous to the previously treated area it was defined as local, otherwise as distant; recurrence classified as Barcelona Clinic Liver Cancer stage C was defined by neoplastic portal vein thrombosis or metastases.

Results

A total of 103 patients were included (82.5% male; median age 70 years, range 39–86). During follow-up, 64 recurrences were observed. Median overall survival was 62 months (95% confidence interval: 54–78) and survival rates were 97%, 65% and 52% at 1, 4 and 5 years, respectively. Median post-recurrence survival was 22 months (95% confidence interval: 16–35). Child–Pugh score, performance status, sum of tumour diameters at recurrence and recurrence patterns were independent predictors of post-recurrence survival.

Conclusions

In patients with hepatocellular carcinoma after radiofrequency ablation, clinical and tumour parameters assessed at relapse, in particular the type of recurrence pattern, influence post-recurrence survival.     

uPA‐uPAR molecular complex is involved in cell signaling during neuronal migration and neuritogenesis

Background: In the development of the central nervous system (CNS), neuronal migration and neuritogenesis are crucial processes for establishing functional neural circuits. This relies on the regulation exerted by several signaling molecules, which play important roles in axonal growth and guidance. The urokinase‐type plasminogen activator (uPA)—in association with its receptor—triggers extracellular matrix proteolysis and other cellular processes through the activation of intracellular signaling pathways. Even though the uPA‐uPAR complex is well characterized in nonneuronal systems, little is known about its signaling role during CNS development. Results : In response to uPA, neuronal migration and neuritogenesis are promoted in a dose‐dependent manner. After stimulation, uPAR interacts with α₅‐ and β₁‐integrin subunits, which may constitute an αβ‐heterodimer that acts as a uPA‐uPAR coreceptor favoring the activation of multiple kinases. This interaction may be responsible for the uPA‐promoted phosphorylation of focal adhesion kinase (FAK) and its relocation toward growth cones, triggering cytoskeletal reorganization which, in turn, induces morphological changes related to neuronal migration and neuritogenesis. Conclusions : uPA has a key role during CNS development. In association with its receptor, it orchestrates both proteolytic and nonproteolytic events that govern the proper formation of neural networks. Developmental Dynamics 243:676–689, 2014. © 2014 Wiley Periodicals, Inc.